Proteomic Profiling of Cervical and Lumbar Spinal Cord Reveals Potential Protective Mechanisms in the Wobbler Mouse, a Model of Motor Neuron Degeneration

摘要

The wobbler mouse is a model of selective motor neuron degeneration in the cervical spinal cord.Comparing cervical and lumbar tracts of control and diseased mice at the early stage of pathology byproteomic analysis, we identified 31 proteins by peptide mass fingerprint after tryptic digestion andMALDI-TOF analysis, that were differently represented among the four experimental groups. In healthymice, patterns of protein expression differed between cervical and lumbar tract: proteins of cellularenergetic metabolism pathway showed lower expression in the cervical tract, while cellular traffickingproteins were overrepresented. In wobbler mice, these differences disappeared and the expressionpattern was similar between cervical and lumbar spinal cord. We found that most of the proteinsdifferentially regulated in wobbler with respect to control cervical tract were related to astrogliosis orinvolved in glutamate-glutamine cycle, energy transduction and redox functions. Proteins over-represented in the wobbler lumbar spinal cord were cytoskeleton proteins and cellular transport proteins,in particular the vesicle fusing ATPase and the isoform 2 of syntaxin-binding protein 1, involved invesicle trafficking. We suggest that overexpression of proteins involved in vesicle trafficking, togetherwith proteins counteracting mitochondria1 dysfunction can have neuroprotective effects, preservinglumbar spinal cord motor neurons in wobbler mice.